LPS-Peptide Interaction in Bladder Inflammation

LPS-肽在膀胱炎症中的相互作用

• 批准号: 7172317
• 负责人: RICARDO SABAN
• 金额: $ 30.56万
• 依托单位: UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-29 至 2009-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7172317
• 关键词: Acute; Adoptive Transfer; Animal Model; Bladder; Bone Marrow; Cell Degranulation; Chronic; Cystitis; Development; End Point; Etiology; F2R gene; Gene Expression; Genes; Grant; Immunohistochemistry; In Situ Hybridization; Inflammation; Inflammatory; Inflammatory Response; Laboratories; Metalloendopeptidases; Methodology; Molecular; Mus; Numbers; Pathway interactions; Pattern; Peptides; Proteinase-Activated Receptors; Publishing; Purpose; RNase protection assay; Research Personnel; Role; Signal Transduction; Stimulus; Substance P; Substance P Receptor; Transcriptional Activation; Tryptase; Up-Regulation; Western Blotting; Zileuton; inhibitor/antagonist; mast cell; programs; receptor; reconstitution

This proposal is a competing continuation of a four year grant which seeks to expand upon the role of mast cells and mast cell products, substance P (SP), and LPS in bladder inflammation and further elucidate the molecular pathways resulting in up-regulation of inflammatory genes. The original specific aims were to determine the role of neutral metalloendopeptidase (NEP), SP receptors, and mast cells in the development of cystitis, utilizing NEP / mice, NK-1R -/ mice, and mast cell deficient mice (kitW/kit_-_), and those which have been reconstituted with mast cells by adoptive transfer from normal mice and NK-1R /- mice. In the present proposal, we seek to expand upon the hypothesis that regardless of the stimuli there is a common intracellular activation pathway of bladder inflammation. We now include the possible role of Protease Activated- Receptors (PAR) as a signaling mechanism owing to tryptase release following mast cell degranulation. There are 6 specific aims in this proposal seeking to determine the role of PARs in the development of acute and chronic bladder inflammation. We will employ methodology and animal models published by this laboratory, including determination of cellular pattern of the 4 different PAR proteins and their gene expression by immunohistochemistry and in situ hybridization. Results will be confirmed by western blotting and quantifiable RNase protection assay developed by this laboratory. The role of PAR in inflammation will be confirmed in PAR ./. mice. In addition, the role of PARs 1 and 2 on mast cells will be determined by examining kitW/kit w-_mice, which are deficient in mast cells, after they receive bone-marrow mast cells from PAR1 -/ or PART/- mice. This study seeks to determine the molecular pathway of acute and chronic bladder inflammation. Information generated by this study should elucidate whether bladder inflammatory responses, regardless of etiology, occur via a common mechanism or whether the endpoints are specific for each stimulus.

这一建议是一个四年赠款的竞争性延续，旨在扩大对桅杆的作用。 细胞和肥大细胞产物，P物质（SP）和LPS在膀胱炎症中的作用，并进一步阐明 导致炎症基因上调的分子途径。最初的具体目标是 确定中性金属内肽酶（NEP），SP受体和肥大细胞在发展中的作用， 膀胱炎，利用NEP /小鼠、NK-1 R-/小鼠和肥大细胞缺陷小鼠（kitW/kit_-_），以及那些 通过从正常小鼠和NK-1 R/-小鼠过继转移用肥大细胞重建。本 建议，我们寻求扩大的假设，无论刺激有一个共同的细胞内 膀胱炎症的激活途径。我们现在包括蛋白酶激活的可能作用- 肥大细胞脱颗粒后类胰蛋白酶释放导致的信号传导机制。 本提案中有6个具体目标，旨在确定PAR在急性 和慢性膀胱炎。我们将采用该出版的方法和动物模型， 实验室，包括测定4种不同PAR蛋白及其基因的细胞模式 免疫组化和原位杂交检测表达。将通过蛋白质印迹法确认结果 和可定量的RNase保护试验。PAR在炎症中的作用将 在PAR ./中确认。小鼠此外，PAR 1和2对肥大细胞的作用将通过以下方式确定： 在接受来自小鼠的骨髓肥大细胞后，检查肥大细胞缺乏的kitW/kit w-_小鼠 PAR 1-/或PART/-小鼠。本研究旨在确定急性和慢性膀胱炎的分子途径， 炎症这项研究产生的信息应该阐明膀胱炎症反应， 无论病因如何，通过共同机制发生，或者终点是否对每种疾病具有特异性 刺激。

项目成果

Regulatory network of inflammation downstream of proteinase-activated receptors.

• DOI: 10.1186/1472-6793-7-3
• 发表时间: 2007-03-30
• 期刊: BMC physiology
• 作者: Saban R;D'Andrea MR;Andrade-Gordon P;Derian CK;Dozmorov I;Ihnat MA;Hurst RE;Simpson C;Saban MR
• 通讯作者: Saban MR

The inflammatory and normal transcriptome of mouse bladder detrusor and mucosa.

• DOI: 10.1186/1472-6793-6-1
• 发表时间: 2006-01-18
• 期刊: BMC physiology
• 作者: Saban, Marcia R;Hellmich, Helen L;Saban, Ricardo
• 通讯作者: Saban, Ricardo

Lymphatic vessel density and function in experimental bladder cancer.

• DOI: 10.1186/1471-2407-7-219
• 发表时间: 2007-11-29
• 期刊: BMC CANCER
• 影响因子: 3.8
• 作者: Saban, Marcia R.;Towner, Rheal;Smith, Nataliya;Abbott, Andrew;Neeman, Michal;Davis, Carole A.;Simpson, Cindy;Maier, Julie;Memet, Sylvie;Wu, Xue-Ru;Saban, Ricardo
• 通讯作者: Saban, Ricardo

Transcription factor network downstream of protease activated receptors (PARs) modulating mouse bladder inflammation.

• DOI: 10.1186/1471-2172-8-17
• 发表时间: 2007-08-17
• 期刊: BMC immunology
• 影响因子: 3
• 作者: Saban R;Simpson C;Davis CA;Dozmorov I;Maier J;Fowler B;Ihnat MA;Hurst RE;Wershil BK;Saban MR
• 通讯作者: Saban MR

cDNA array of lipopolysaccharide-induced bladder gene expression.

脂多糖诱导的膀胱基因表达的cDNA阵列。

• DOI: 10.1016/s0090-4295(01)01064-0
• 发表时间: 2001
• 期刊: Urology
• 影响因子: 2.1
• 作者: Saban,MR;Nguyen,NB;Hammond,TG;Saban,R
• 通讯作者: Saban,R